The mechanisms by which the nervous system recovers from injury are of tremendous interest, and understanding these processes may lead to clinical approaches to facilitating such recovery. Research on the development and regeneration of the neuromuscular system has made this one of the premiere model systems for studies of neuronal recovery from injury. One intriguing and unexplained observation is that the developing neuromuscular system is less capable of functional recovery than is the mature neuromuscular system. Recent work suggests that Schwann cells induce motoneurons to sprout and provide substrates for nerve growth. Furthermore, nerve injury during early postnatal life, but not in adulthood, results in Schwann cell death. Terminal Schwann cells, therefore, may play a critical role in successful reinnervation and may underlie developmental differences in the neuromuscular response to nerve injury. The present research proposal focuses on the response of developing and mature motoneurons to partial denervation, and the possible importance of terminal Schwann cells in this response. The proposed studies will use a variety of techniques, including immunohistochemistry, electrophysiology, and targeted cell ablations in transgenic animals, to achieve the following specific aims: (1) to examine the response of neonatal motoneurons to denervation of nearby muscle fibers (partial denervation) and (2) to experimentally determine the role played by terminal Schwann cells in reinnervation after partial denervation.